Discovery of Butyrylcholinesterase-Activated Near-Infrared Fluorogenic Probe for Live-Cell and<i>In Vivo</i>Imaging
Why this work is in the frame
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Bibliographic record
Abstract
Butyrylcholinesterase (BChE) is widely distributed in various tissues and highly implicated in several important human diseases, especially Alzheimer's disease (AD). However, the role of BChE in AD is still controversial, which may be partially attributed to the lack of a direct tool for real-time and noninvasive monitoring of BChE in in vivo. Here, we report three rationally designed near-infrared fluorogenic probes that possess excellent discrimination for butyrylcholinesterase (BChE) over the related enzyme acetylcholinesterase (AChE). The refined probe, BChE-NIRFP, not only functions as an exquisite substrate for BChE in in vitro assays but also represents a superb "signal-on" imaging tool to real-time track BChE levels in human cells, zebrafish, and a mouse model of AD. A further application of BChE-NIRFP to identify the cellular mechanism reveals that Aβ fibrils and insulin resistance may be important contributors to the abnormally elevated BChE levels observed during AD progression. Based on the results from the present study, this new probe is a valuable tool for basic and clinical research designed to obtain a complete understanding of the physiological roles of BChE in diverse human diseases, particularly AD.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it